Development of a World Health Organization International Reference Panel for different genotypes of hepatitis E virus for nucleic acid amplification testing.

Globally, hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Epidemiology and clinical presentation of hepatitis E vary greatly by location and are affected by the HEV genotype. Nucleic acid amplification technique (NAT)-based assays are important for the detection of acute HEV infection as well for monitoring chronic cases of hepatitis E. The aim of the study was to evaluate a panel of samples containing different genotypes of HEV for use in nucleic NAT-based assays. The panel of samples comprises eleven different members including HEV genotype 1a (2 strains), 1e, 2a, 3b, 3c, 3e, 3f, 4c, 4g as well as a human isolate related to rabbit HEV. Each laboratory assayed the panel members directly against the 1 World Health Organization (WHO) International Standard (IS) for HEV RNA (6329/10) which is based upon a genotype 3 a strain. The samples for evaluation were distributed to 24 laboratories from 14 different countries and assayed on three separate days. Of these, 23 participating laboratories returned a total of 32 sets of data; 17 from quantitative assays and 15 from qualitative assays. The assays used consisted of a mixture of in-house developed and commercially available assays. The results showed that all samples were detected consistently by the majority of participants, although in some cases, some samples were detected less efficiently. Based on the results of the collaborative study the panel (code number 8578/13) was established as the "1st International Reference Panel (IRP) for all HEV genotypes for NAT-based assays" by the WHO Expert Committee on Biological Standardization. This IRP will be important for assay validation and ensuring adequate detection of different genotypes and clinically important sub-genotypes of HEV

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Structural brain correlates of childhood inhibited temperament: an ENIGMA-Anxiety Mega-analysis

NWORubicon 019.201SG.022Pathways through Adolescenc

Messaging Matters: The Impact of Advising Micromessages on Student Affect and Behavior across Diverse University Campuses

Across two experimental university studies, we examined how small changes in language embedded in advising communications influence student outcomes (e.g., support, persistence) and explored the utility of advising micromessages congruent with growth mindset and appreciative advising for diverse student populations. We found that micromessages embedded within hypothetical advisor emails increased anticipated positive student outcomes, including feelings of support and persistence. In line with our hypotheses and attribution-based intervention research with nontraditional and/or marginalized students, the positive effect of micromessaging appears greater for first-generation students and students of color. This research highlights opportunities to shape consequential student outcomes through small, strategic language changes. Empowering advisors with thoughtfully crafted language improves students' sense of support and persistence and may reduce achievement gaps

Stepping stones or stone dead? : fecundity, pollen dispersal and mating patterns of roadside qualea grandiflora mart. trees

Forest fragmentation may affect mating and pollen dispersal patterns through conversion of continuous forests into small, spatially isolated remnant patches and individual trees in an anthropogenic landscape. We investigated reproductive investment and success, pollen dispersal, mating system, and genetic diversity and spatial structure of Qualea grandiflora trees in two environmental contexts: a continuous natural Cerrado area and isolated individuals on roadsides. Roadside trees produced more flowers and more fruit than Cerrado trees. Pollen dispersal kernels were fat-tailed in both contexts, indicating long-distance dispersal, but in Cerrado the mean pollen dispersal distance (524.7 m) and the effective number of pollen donors per mother-tree (Nep = 12.7) were higher than for roadside trees (60.9 m, Nep = 4.6). The levels and structure of genetic diversity, outcrossing rates (tm > 0.98), and mating among relatives (tm−ts < 0.1) were similar in both environmental contexts. Allelic richness and number of private alleles were similar between the two environments. The fixation index was significantly lower in adults (minimum of 0.08) than in offspring (minimum of 0.23) in both contexts, suggesting selection against inbred individuals between offspring and adult stage. Our results indicate that the spatial isolation of roadside trees, by increasing the number of flowers produced, decreased pollinator movements, thereby reducing effective pollen flow and the number of pollen donors. All these results suggest that roadside trees can be used for harvesting seeds for recovery plans, and that these trees are a biological legacy, and reservoir of Q. grandiflora genetic diversity, from the original Cerrado forest20613551367CNPQ - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPESP – Fundação de Amparo à Pesquisa Do Estado De São PauloNão tem2014/17472-